IsoBED: a tool for automatic calculation of biologically equivalent fractionation schedules in radiotherapy using IMRT with a simultaneous integrated boost (SIB) technique

Radiotherapy and Oncology

McDonald

et al. 2017

100

Background and Purpose Regional differences in sensitivity to white matter damage after brain radiotherapy (RT) are not well-described. We characterized the spatial heterogeneity of dose-response across white matter tracts using diffusion tensor imaging (DTI). Materials and Methods Forty-nine patients with primary brain tumors underwent MRI with DTI before and 9–12 months after partial-brain RT. Maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were generated. Atlas-based white matter tracts were identified. A secondary analysis using skeletonized tracts was also performed. Linear mixed-model analysis of the relationship between mean and max dose and percent change in DTI metrics was performed. Results Tracts with the strongest correlation of FA change with mean dose were the fornix (−0.46 percent/Gy), cingulum bundle (−0.44 percent/Gy), and body of corpus callosum (−0.23 percent/Gy), p<.001. These tracts also showed dose-sensitive changes in MD and RD. In the skeletonized analysis, the fornix and cingulum bundle remained highly dose-sensitive. Maximum and mean dose were similarly predictive of DTI change. Conclusions The corpus callosum, cingulum bundle, and fornix show the most prominent dose-dependent changes following RT. Future studies examining correlation with cognitive functioning and potential avoidance of critical white matter regions are warranted.

Section: Methodsmentioning

confidence: 99%

Regional susceptibility to dose-dependent white matter damage after brain radiotherapy

Connor

Radiotherapy and Oncology

McDonald

et al. 2017

100

“…Radiation dose for the other 10 patients was converted at each voxel location in the volume to a 30-fraction equivalent for direct comparison. Dose conversion was achieved using principles of biologically equivalent dose and an alpha/beta ratio of 2 Gy (15, 16). …”

Section: Methodsmentioning

confidence: 99%

Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

Seibert

International Journal of Radiation Oncology*Biology*Physics

Bartsch

et al. 2017

Purpose/Objectives Following brain radiation therapy (RT), patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Materials/Methods Hippocampal volume was measured with MRI in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3D volumetric MRI prior to and one year post-RT. Images were processed using software with FDA clearance and CE (Conformité Européene) marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy one year post-RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α=0.05. Results Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, p=0.03). Mean hippocampal volume was significantly reduced one year after high-dose RT (mean −6%, p=0.009), but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (p<0.01). Conclusions The hippocampus demonstrates radiation dose-dependent atrophy following treatment for brain tumors. Quantitative MRI is a non-invasive imaging technique capable of measuring radiation effects on intracranial structures. This technique could be investigated as a potential biomarker for development of reliable dose constraints for improved cognitive outcomes.

“…All patients were treated to 60 Gy in 30 fractions except for two: one was treated to 40.05 Gy in 15 fractions, and the other to 59.4 Gy in 33 fractions. These schedules were converted to a total equivalent dose in standard 2 Gy fractionation using biologically equivalent dose principles [20] and an α/β ratio of 2 Gy [21]. Treatment and demographic factors are shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Dose-dependent white matter damage after brain radiotherapy

Connor

Radiotherapy and Oncology

McDonald

et al. 2016

102

107

Background and Purpose Brain radiotherapy is limited in part by damage to white matter, contributing to neurocognitive decline. We utilized diffusion tensor imaging (DTI) with multiple b-values (diffusion weightings) to model the dose-dependency and time course of radiation effects on white matter. Materials and Methods Fifteen patients with high-grade gliomas treated with radiotherapy and chemotherapy underwent MRI with DTI prior to radiotherapy, and after months 1, 4-6, and 9-11. Diffusion tensors were calculated using three weightings (high, standard, and low b-values) and maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ‖), and radial diffusivity (λ⊥) were generated. The region of interest was all white matter. Results MD, λ‖, and λ⊥increased significantly with time and dose, with corresponding decrease in FA. Greater changes were seen at lower b-values, except for FA. Time-dose interactions were highly significant at 4-6 months and beyond (p < .001), and the difference in dose response between high and low b-values reached statistical significance at 9-11 months for MD, λ‖, and λ⊥ (p < .001, p < .001, p = .005 respectively) as well as at 4-6 months for λ‖ (p = .04). Conclusions We detected dose-dependent changes across all doses, even <10 Gy. Greater changes were observed at low b-values, suggesting prominent extracellular changes possibly due to vascular permeability and neuroinflammation.